Thursday, December 10, 2009

Last week's NEJM has the results of a trial of a continuous flow left ventricular device for advanced heart failure. For those of you unfamiliar with LVADs, essentially they are implanted pumps which are inserted directed into the heart and major vessels which pump blood and 'take-over' for the heart; they are partially external (e.g. a battery/power pack is external to the body) - a basic intro, with pictures, is here. Historically they were used to keep patients alive while awaiting heart transplantation. More and more, however, they are being used 'permanently' - to keep patients alive longer, even with no expectation of transplantation. Although costly, and associated with a lot of risks and complications, comparative trials of LVADs with 'medical management' have indicated they can prolong life and improve health related quality of life, in select patients. For a concise summary of the previous data and discussion about LVADs & palliative care, see this Fast Fact; while indeed life-prolonging, a large majority of patients die within 2 years.

This study, a randomized controlled trial, compared outcomes for 200 patients with advanced heart failure (these were sick patients - EF less than 25%, disabling dyspnea/angina at rest or with minimal exertion, nearly 80% receiving inotropes at the time of enrollment, etc.) who were randomized to either a device with a newer design ('continuous flow') or a standard LVAD (which they describe as 'pulsatile-flow' devices). For brevity, I'll use cLVAD and pLVAD in this post. All were ineligible for a transplant at the time of enrollment, although a few ended up receiving transplanted hearts. The authors describe the differences between the devices as such (and there are reasonably understandable diagrams in the paper itself if you're interested):

First-generation devices are pulsatile-displacementpumps that provide blood flow in a fashion analogous to thatin the native heart. Such pumps are limited by size and durability,since pulsatility necessitates the mechanical wear of the ventricularassist device. Continuous-flow pumps have small rotating impellersthat propel blood forward with surprisingly little hematologictrauma and can do so with greater durability and a smaller size(about the size of a D battery) than pulsatile-flow devices,since there is only a single moving part. Newer pumps use bearing-freedesigns to minimize device wear.

The primary outcome was survival at 2 years without disabling stroke or need for re-operation, and an intention to treat analysis was used. Patients were followed regularly for the 2 years. The device manufacturer funded the study.

Gross survival was better in the cLVAD group: 1 & 2 year survivals of 68% and 58% vs. 55% and 24% for pLVAD patients. Only 2 patients were alive in the pLVAD group who had the original pumps (most died - the remainder had new pumps or received heart transplants). 46% of the cLVAD patients met the combined primary end point at 2 years vs. 11% for the pLVAD patients: the differences were due to survival, clearly, as well as need for re-operation (36% for pLVAD vs 10% for cLVAD). About 11% in both groups suffered disabling strokes.

Health-related quality of life improved in both groups, about the same (all of this measured by summative HRQOL indices). The burden of therapy was reduced in the cLVAD group, fewer rehospitalizations/surgeries, 88% of time spent outside of a hospital post implantation vs. 74% for the pLVAD, etc. They describe the cause of death in the patients, although not in sufficient detail to really understand what happened - approximately a third of all deaths were from hemorrhagic strokes, however. It looks like about 12% of the deaths in the cLVAD group were from 'external power interruption' which is chilling to contemplate.

While all of this sounds excellent, it's important to realize these were well-selected patients, and while the paper describes inclusion and exclusion criteria, it's unclear (for these 200 patients) what the true denominator was - how many for instance were screened (e.g. end stage heart failure patient hospitalized on inotropes) and excluded prior to enrollment (due to comorbidities or unwillingness to have an LVAD, etc.) - ie this is not a therapy that will be available for many (?most) end stage heart failure patients.

I think of VADs as being paradigmatic of the promises of 21st century, technologically focused medicine. Expensive, constantly changing, and able to keep people alive for a real amount of time - improving 2 year survival from ~10% (which is the survival in the LVAD trials for those who received medical management) to, now, over 50%, improving (at least health-related) quality of life and symptoms, but with much morbidity (strokes, walking around with a battery pack plugged, through your skin, into a pump in your abdomen and chest). Nonetheless the survival advantage is marked and much, much better than most of the latest, fancy 'targeted therapies' for cancer, with an improvement in HRQOL to boot.

My vague enthusiasm aside, there is something which makes me quesy about LVADs, and it's not just the cyborg aspect to them. I wonder if it's also because they challenge, to an extend, some common perceptions about appropriate care for patients with incurable and terminal illnesses. It may be that what's true of - for example - cancer, and dementia, and end stage renal disease (in older, frail patients - see my recent post about this here), is not true with cardiac pump failure. That is, that stepping up invasive, costly medical interventions generally (and of course this is all speaking generally) do very little for our patients: prolong life only marginally (e.g. 'targeted' therapy or long-shot chemotherapy in advanced cancer patients), or at the cost of quality of life by actively worsening it, or by not stopping it from deteriorating (e.g. basically anything we do to prolong life in end stage dementia; dialysis in frail older adults which is life-prolonging but often not 'restorative'). You get the point - this is the stuff we deal with everyday in palliative care.

But, damn, it looks like LVADs might be different - people feel better, and live longer, albeit with still with prognoses shorter than most cancers, and with a sudden/catastrophic death looming over them.

Which has me wondering - how do these patients actually die? Where (ie ICU vs. hospital vs. home)? And how much control do they have other the circumstances? LVAD pumping vs. not vs. explanted? How 'prepared' are patients, and families (for dying, for the choices they will face, for what occurs when the LVAD fails or something else goes wrong)? We don't see many of these patients at my institution, although I know there are scattered palliative care programs nationally who see a lot of LVAD patients - and I'd appreciate any observations about this. In some ways this population seems made for palliative care (symptom management, care planning coincident with seeking aggressive life-prolonging treatments), but I also wonder if as a group the patients are similar to the (speaking in gross generalizations here I know) Phase I trial cancer patients - fiercely seeking any opportunity for life prolongation, and not particularly interested in contemplating Plan B. Certainly, 'palliative care' is no where to be found in the research paper or the editorial.

You can read the article yourself - it's disquieting to say the least, even if the comparison with P&P is a little overbearing. It does give a sense however of what it's like to live with an LVAD: stigma, feeling trapped by the VAD's battery life, loss of control by the intense medicalization of your life, living in fear of death or a complication. Realities, and challenges, not captured by the summative HRQOL scales in the NEJM study.

Pallimed: A Hospice & Palliative Medicine Blog Founded June 8, 2005.
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